Objectives: Studies of saccadic eye movement impairment in Alzheimer’s disease (AD) have largely focused on simple reflexive eye movements and the antisaccade task. The effects of manipulating stimulus timing have been little studied. Methods: Fourteen patients with mild to severe AD and 11 age-matched controls were studied on the antisaccade task, while latencies on simultaneous, gap and predictable tasks were recorded from 11 patients and 11 controls. Dementia severity was assessed with the Mini-Mental State Examination. Results: As a group, patients’ latencies were significantly higher and more variable on the simultaneous and gap tasks. Predictable task performance was similar in mean but significantly more variable. Grossly anticipatory responses by patients were common on the predictable, simultaneous and gap tasks. Exclusion of these from subject means revealed that AD patients, when making target-driven saccades, demonstrated a gap effect of similar magnitude to normal subjects. Patients made significantly fewer correct antisaccades and significantly more reflexive errors not followed by a corrective antisaccade than did controls. Conclusions: The frequent presence of grossly anticipatory saccades may reflect dysfunction of fixation mechanisms possibly involving projections from frontal lobe to superior colliculus. The less frequently seen, marked prolongation of latency may reflect changes in posterior parietal mechanisms mediating reflexive saccade generation. The presence of the gap effect demonstrates a continued ability to benefit from externally controlled stimulus disengagement. Patients’ ability to make appropriately timed saccades to targets of known locations was particularly impaired, but the target sequence itself was at least grossly correctly learned. Larger studies may be able to identify clinically distinct populations of AD patients.

Fletcher WA, Sharpe JA: Saccadic eye movement dysfunction in Alzheimer’s disease. Ann Neurol 1986;20:464–471.
Currie J, Ramsden B, McArthur C, Maruff P: Validation of a clinical antisaccadic eye movement test in the assessment of dementia. Arch Neurol 1991;48:644–648.
Scinto LFM, Daffner KR, Castro L, Weintraub S, Vavrik M, Mesulam MM: Impairments of spatially directed attention in patients with probable Alzheimer’s disease as measured by eye movements. Arch Neurol 1994;51:682–688.
Bylsma FW, Rasmusson DX, Rebok GW, Keyl PM, Tune L, Brandt J: Changes in visual fixation and saccadic eye movements in Alzheimer’s disease. Int J Psychophysiol 1995;19:33–40.
Hotson JR, Steinke GW: Vertical and horizontal saccades in aging and dementia: Failure to inhibit anticipatory saccades. Neuroophthalmology 1988;8:267–273.
Jones A, Friedland RP, Koss B, Stark L, Thompkins-Ober BA: Saccadic intrusions in Alzheimer-type dementia. J Neurol 1983;229:189–194.
Pirozzolo FJ, Hansch EC: Oculomotor reaction time in dementia reflects degree of cerebral dysfunction. Science 1981;214:349–351.
Hershey LA, Whicker L, Abel LA, Dell’Osso LF, Traccis S, Grossniklaus D: Saccadic latency measurements in dementia. Arch Neurol 1983;40:592–593.
Moser A, Kompf D, Olschinka J: Eye movement dysfunction in dementia of the Alzheimer type. Dementia 1995;6:264–268.
Kuskowski MA, Malone SM, Mortimer JA, Dysken MW: Smooth pursuit eye movements in dementia of the Alzheimer type. Alzheimer Dis Assoc Disord 1989;3:157–171.
Fletcher WA, Sharpe JA: Smooth pursuit dysfunction in Alzheimer’s disease. Neurology 1988;38:272–277.
Hutton JT: Eye movements and Alzheimer’s disease: Significance and relationship to visuospatial confusion; in Hutton JT, Kenny AD (eds): Senile Dementia of the Alzheimer Type. New York, Liss, 1985, pp 3–33.
Daffner KR, Scinto LFM, Weintraub S, Guinessey JE, Mesulam MM: Diminished curiosity in patients with probable Alzheimer’s disease as measured by exploratory eye movements. Arch Neurol 1992;42:320–328.
Daffner KR, Mesulam MM, Cohen LG, Scinto LF: Mechanisms underlying diminished novelty-seeking behavior in patients with probable Alzheimer’s disease. Neuropsychiatry Neuropsychol Behav Neurol 1999;12:58–66.
Csibra G, Johnson MH, Tucker LA: Attention and oculomotor control: A high-density ERP study of the gap effect. Neuropsychologia 1997;35:855–865.
Kingstone A, Klein RM: Visual offsets facilitate saccadic latency: Does predisengagement of visuospatial attention mediate this gap effect? J Exp Psychol Hum Percept Perform 1993;19:1251–1265.
Reuter-Lorenz PA, Hughes HC, Fendrich R: The reduction of saccadic latency by prior offset of the fixation point: An analysis of the gap effect. Percept Psychophys 1991;49:167–175.
Fischer B, Breitmeyer B: Mechanisms of visual attention revealed by saccadic eye movements. Neuropsychologia 1987;25:73–83.
Munoz DP, Broughton JR, Goldring JE, Armstrong IT: Age-related performance of human subjects on saccadic eye movement tasks. Exp Brain Res 1998;121:391–400.
McKhann G, Drachmann D, Folstein M, Katzman R, Price D, Stadlan EM: Clinical diagnosis of Alzheimer’s disease: Report of the NINCDS-ADRDA Work Group under the auspices of the Department of Health and Human Services Task Force on Alzheimer’s Disease. Neurology 1984;34:939–944.
Davis KL, Powchik P: Tacrine. Lancet 1995;345:625–630.
Burback D, Molnar FJ, St John P, Man-Son-Hing M: Key methodological features of randomized controlled trials of Alzheimer’s disease therapy. Minimal clinically important difference, sample size and trial duration. Dement Geriatr Cogn Disord 1999;10:534–540.
Eguchi J, Saitoh Y, Egawa M, Saito KI, Kawamura H: MCI-225, a novel thienopyrimidine analog, enhances attentional eye tracking in midpontine pretrigeminal preparation. Pharmacol Biochem Behav 1997;56:229–234.
Almkvist O, Jelic V, Amberla K, Hellstrom-Lindahl E, Meurling L: Responder characteristics to a single oral dose of cholinesterase inhibitor: A double-blind placebo-controlled study with tacrine in Alzheimer patients. Dement Geriatr Cogn Disord 2001;12:22–32.
Nordberg A, Amberla K, Shigeta M, Lundqvist H, Viitanen M, Hellstrom-Lindahl E, Johannson M, Andersson J, Hartvig P, Lilja A, Langstrom B, Winblad B: Long-term tacrine treatment in three mild Alzheimer patients: Effects on nicotinic receptors, cerebral blood flow, glucose metabolism, EEG, and cognitive abilities. Alzheimer Dis Assoc Disord 1998;12:228–237.
Guitton D, Buchtel HA, Douglas RM: Frontal lobe lesions in man cause difficulties in suppressing reflexive glances and in generating goal-directed saccades. Exp Brain Res 1985;58:455–472.
Folstein MF, Folstein SE, McHugh PR: Mini-Mental State: A practical method for grading the cognitive state of patients for the clinician. J Psychiat Res 1975;12:189–198.
Braun D, Weber H, Mergner T, Schulte-Monting J: Saccadic reaction times in patients with frontal and parietal lesions. Brain 1992;115:1359–1386.
Zackon DH, Sharpe JA: Smooth pursuit in senescence. Acta Otolaryngol (Stockh) 1987;104:290–297.
Warabi T, Kase M, Kato T: Effect of aging on the accuracy of visually guided saccadic eye movement. Ann Neurol 1984;16:449–454.
Sharpe JA, Sylvester TO: Effects of aging on horizontal smooth pursuit. Invest Ophthalmol Vis Sci 1978;17:465–468.
Abel LA, Troost BT, Dell’Osso LF: The effects of age on normal saccadic characteristics and their variability. Vision Res 1983;23:33–37.
Carlesimo GA, Oscar-Berman M: Memory deficits in Alzheimer’s patients: A comprehensive review. Neuropsychol Rev 1992;3:119–169.
Posner MI, Walker JA, Friedrich FJ, Rafal RD: Effects of parietal injury on covert orienting of attention. J Neurosci 1984;4:1863–1874.
Tam WJ, Stelmach LB: Viewing behavior: Ocular and attentional disengagement. Percept Psychophys 1993;54:211–222.
Tian JR, Zee DS, Lasker AG, Folstein SE: Saccades in Huntington’s disease: Predictive tracking and interaction between release of fixation and initiation of saccades. Neurology 1991;41:875–881.
Ross SM, Ross LE: Children’s and adults’ predictive saccades to square-wave targets. Vision Res 1987;27:2177–2180.
Stark L, Vossius G, Young LR: Predictive control of eye tracking movements. IRE Trans Hum Factors Elect 1962(HFE-3):52–57.
Bronstein AM, Kennard C: Predictive ocular motor control in Parkinson’s disease. Brain 1985;108:925–940.
Sharpe JA: Adaptation to frontal lobe lesions; in Keller EL, Zee DS (eds): Adaptive Processes in Visual and Oculomotor Systems. Oxford, Pergamon Press, 1986, pp 239–246.
Biscaldi M, Fischer B, Stuhr V: Human express saccade makers are impaired at suppressing visually evoked saccades. J Neurophysiol 1996;76:199–214.
Gaymard B, Ploner CJ, Rivaud-Pechoux S, Pierrot-Deseilligny C: The frontal eye field is involved in spatial short-term memory but not in reflexive saccade inhibition. Exp Brain Res 1999;129:288–301.
O’Driscoll GA, Alpert NM, Matthysse SW, Levy DL, Rauch SL, Holzman PS: Functional neuroanatomy of antisaccade eye movements investigated with positron emission tomography. Proc Natl Acad Sci USA 1995;92:925–929.
Paus T, Kalina M, Patockova L, Angerova Y, Cerny R, Mecir P, Bauer J, Krabec P: Medial vs. lateral frontal lobe lesions and differential impairment of central-gaze fixation maintenance in man. Brain 1991;114:2051–2067.
Sweeney JA, Mintun MA, Kwee S, Wiseman MB, Brown DL, Rosenberg DR, Carl JR: Positron emission tomography study of voluntary saccadic eye movements and spatial working memory. J Neurophysiol 1996;75:454–468.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.